Genetic Aspects: Viral Oncogenesis In Wild Mouse Species

各种野生小鼠和近交系小鼠在对逆转录病毒和逆转录病毒诱导的疾病的易感性方面彼此不同。这些差异是由于特定小鼠染色体基因中的等位基因差异，我们一直在努力识别和表征参与这种抗性的小鼠基因。今年，我们一直在描述一种在大多数小鼠中发现的血清脂蛋白因子，它能灭活白血病病毒。我们已经确定，这种因子的存在是在一个单一的基因，映射到远端小鼠染色体10的控制。我们已经注意到它与一个很好的候选基因载脂蛋白F有密切的物理联系，我们已经评估了载脂蛋白F作为这个血清因子的可能候选基因。在另一项研究中，我们还继续努力表征抗性基因Rmcf，其负责对多变类MLV的部分抗性。我们现在已经克隆了与Rmcf基因座相关的病毒包膜的染色体整合拷贝，并且该基因的序列分析表明它与先前在Rmcf阳性菌株DBA小鼠中检测到的不寻常的病毒包膜糖蛋白相同。这表明Rmcf抗性可能通过干扰机制介导。我们还开始了一项研究，以检查在野生小鼠中发现的白血病病毒基因的染色体整合拷贝。我们已经将莫洛尼白血病病毒引入这些小鼠，并回收了具有新生长特性的病毒。我们正在对这些回收的重组病毒进行测序，以确定其不寻常特性的基础。最后，我们与J.达德利博士合作研究TBLV，这是一种诱导淋巴瘤的乳腺肿瘤病毒衍生物。我们证明了肿瘤的诱导与癌基因myc附近的病毒插入有关，但这种插入发生在与淋巴瘤诱导白血病病毒不同的位置。

The various wild mice and inbred strains differ from one another in their susceptibility to retroviruses and retrovirus-induced diseases. These differences are due to allelic differences in specific mouse chromosomal genes, and we have been engaged in an ongoing effort to identify and characterize the mouse genes involved in this resistance. This year, we have been characterizing a serum lipoprotein factor found in most mice that inactivates leukemia viruses. We have determined that the presence of this factor is under control of a single gene that maps to distal mouse Chromosome 10. We have noted its close physical linkage to a good candidate gene, apolipoprotein F, and we have evaluated ApoF as a possible candidate for this serum factor. In another study, we have also continued our efforts to characterize the resistance gene Rmcf, which is responsible for partial resistance to the polytropic class of MLVs. We have now cloned a chromosomally integrated copy of the viral envelope associated with the Rmcf locus, and sequence analysis of this gene indicates it is identical to an unusual viral envelope glycoprotein previously detected in the Rmcf positive strain DBA mice. This suggests Rmcf resistance may be mediated through an interference mechanism. We have also initiated a study to examine the chromosomally integrated copies of leukemia virus genes found in wild mice. We have introduced Moloney leukemia virus into these mice and recovered viruses with novel growth properties. We are in the process of sequencing these recovered recombinant viruses to determine the basis for their unusual properties. Finally, we have collaborated with Dr. J. Dudley on TBLV, a mammary tumor virus derivative that induces lymphomas. We demonstrated that tumor induction is associated with virus insertion near the oncogene myc, but that insertion occurs at a location distinct from that of the lymphoma unducing leukemia viruses.